中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2500110080
最近更新日期： Date of Last Refreshed on：	2025-09-30 08:27:14
注册时间： Date of Registration：	2025-09-30 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	TACE联合MWA术后短疗程辅助替雷利珠单抗治疗BCLC 0 –B期HCC的有效性和安全性研究
Public title：	Efficacy and Safety of Short-Course Adjuvant Tislelizumab Following TACE Combined with MWA in Patients with BCLC Stage 0–B Hepatocellular Carcinoma
注册题目简写：
English Acronym：
研究课题的正式科学名称：	TACE联合MWA术后短疗程辅助替雷利珠单抗治疗BCLC 0 –B期HCC的有效性和安全性研究
Scientific title：	Efficacy and Safety of Short-Course Adjuvant Tislelizumab Following TACE Combined with MWA in Patients with BCLC Stage 0–B Hepatocellular Carcinoma
研究课题代号(代码)： Study subject ID：
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：

申请注册联系人：	张松男	研究负责人：	张松男
Applicant：	Songnan Zhang	Study leader：	Songnan Zhang
申请注册联系人电话： Applicant telephone：	+86 155 2677 1553	研究负责人电话： Study leader's telephone：	+86 155 2677 1553
申请注册联系人传真： Applicant Fax：		研究负责人传真： Study leader's fax：
申请注册联系人电子邮件： Applicant E-mail：	zhangsn21@163.com	研究负责人电子邮件： Study leader's E-mail：	zhangsn21@163.com
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	吉林省延吉市局子街1327号	研究负责人通讯地址：	吉林省延吉市局子街1327号
Applicant address：	1327 Juzi Strueet, Yanji, Jilin, China	Study leader's address：	1327 Juzi Strueet, Yanji, Jilin, China
申请注册联系人邮政编码： Applicant postcode：		研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	延边大学附属医院
Applicant's institution：	Affiliated Hospital of Yanbian University
研究负责人所在单位：	延边大学附属医院
Affiliation of the Leader：	Affiliated Hospital of Yanbian University

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	延医伦理20250006号	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	延边大学附属医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Yanbian University Affiliated Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-08-25 00:00:00
伦理委员会联系人：	熊焕章
Contact Name of the ethic committee：	Yanxiang Liu
伦理委员会联系地址：	吉林省延吉市局子街1327号
Contact Address of the ethic committee：	1327 Juzi Strueet, Yanji, Jilin, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 155 2677 1786	伦理委员会联系人邮箱： Contact email of the ethic committee：

研究实施负责（组长）单位：

延边大学附属医院

Primary sponsor：

Affiliated Hospital of Yanbian University

研究实施负责（组长）单位地址：

吉林省延吉市局子街1327号

Primary sponsor's address：

1327 Juzi Strueet, Yanji, Jilin, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	吉林	市(区县)：	延吉
Country：	China	Province：	Jilin	City：	Yanji
单位(医院)：	延边大学附属医院	具体地址：	吉林省延吉市局子街1327号
Institution hospital：	Affiliated Hospital of Yanbian University	Address：	1327 Juzi Strueet, Yanji, Jilin, China

经费或物资来源：

自筹

Source(s) of funding：

raised by researchists

研究疾病：

BCLC 0 –B期HCC

Target disease：

BCLC Stage 0–B Hepatocellular Carcinoma

研究疾病代码：

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

II期临床试验

Study phase：

2

研究设计：

连续入组

Study design：

Sequential

研究目的：

主要研究目的：通过评估无复发生存期（RFS）来评价BCLC 0-B期HCC在TACE联合MWA后接受短疗程替雷利珠单抗辅助治疗的有效性。次要研究目的：通过评估总生存期（OS）、局部复发率（LTP）、肝内远处复发率（IDR）、肝外复发时间（TTED）来评价BCLC 0-B期HCC在TACE联合MWA后接受短疗程替雷利珠单抗辅助治疗的有效性。评价BCLC 0-B期HCC在TACE联合MWA后接受短疗程替雷利珠单抗辅助治疗的安全性。探索性研究目的：探索潜在预测肝癌复发的生物标志物，包括外周血肿瘤相关外泌体的检测、富集、表型鉴定及筛查肿瘤特异性标记物，评估与复发的相关性。

Objectives of Study：

Primary Objective To evaluate the efficacy of short-course adjuvant Tislelizumab following TACE combined with MWA in patients with BCLC stage 0–B hepatocellular carcinoma (HCC), as assessed by recurrence-free survival (RFS). Secondary Objectives To further assess the efficacy of short-course adjuvant toripalimab following TACE combined with MWA in BCLC stage 0–B HCC by evaluating overall survival (OS), local tumor progression (LTP), intrahepatic distant recurrence (IDR), and time to extrahepatic dissemination (TTED). To evaluate the safety of short-course adjuvant Tislelizumab following TACE combined with MWA in BCLC stage 0–B HCC. Exploratory Objective To explore potential biomarkers predictive of HCC recurrence, including detection, enrichment, and phenotypic characterization of tumor-associated exosomes in peripheral blood, as well as screening for tumor-specific markers and assessing their correlation with recurrence.

药物成份或治疗方案详述：

本研究旨在评估短疗程辅助替雷利珠单抗在 BCLC 0–B 期 HCC 患者 TACE 联合 MWA 治疗后的疗效与安全性。接受TACE联合MWA治疗的BCLC 0-B期的HCC患者，治疗1周后复查影像学，依据 mRECIST 标准确认完全缓解（CR）方可入组，签署知情同意后，经筛选符合入排标准。所有患者均接受短疗程（6个月）替雷利珠单抗（200mg，每3周1次）。

Description for medicine or protocol of treatment in detail：

This study aims to evaluate the efficacy and safety of short-course adjuvant Tislelizumab in patients with BCLC stage 0–B hepatocellular carcinoma (HCC) following treatment with TACE combined with MWA. Patients with BCLC stage 0–B HCC who underwent TACE plus MWA were reassessed by imaging one week after treatment, and only those achieving complete response (CR) as defined by the mRECIST criteria were eligible for enrollment. After providing written informed consent and meeting all inclusion and exclusion criteria, eligible patients received short-course adjuvant Tislelizumab (200 mg every 3 weeks for a total duration of 6 months).

纳入标准：

Inclusion criteria

1. Written informed consent must be signed prior to any trial-related procedures;
2. Male or female, aged >=18 years;
3. Hepatocellular carcinoma (HCC) confirmed by imaging or histopathology;
4. Barcelona Clinic Liver Cancer (BCLC) stage 0–B;
5. Patients who previously underwent surgical resection or curative ablation, with recurrence occurring more than 2 years after the initial treatment;
6. No vascular invasion or extrahepatic metastasis;
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0–1;
8. Estimated life expectancy >6 months;
9. Adequate organ function, defined as meeting the following laboratory criteria:
    Absolute neutrophil count (ANC) >=1.5 × 10^9/L without granulocyte colony-stimulating factor use within 14 days prior to testing;
    Platelet count >=75 × 10^9/L without transfusion within 14 days;
    Hemoglobin >9 g/dL without blood transfusion or erythropoietin within 14 days;
    Total bilirubin <=1.5 × the upper limit of normal (ULN);
    Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=3 × ULN;
    Serum creatinine <=1.5 × ULN and creatinine clearance (calculated by Cockcroft–Gault formula) >=50 mL/min;
    International normalized ratio (INR) <=2.3 or prothrombin time (PT) <=6 seconds above the upper limit of normal;
    Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the reference range; if baseline TSH is outside the normal range, patients may still be eligible if total T3 (or FT3) and FT4 are within normal limits;
    Normal cardiac enzyme levels (patients with isolated, clinically insignificant laboratory abnormalities as judged by the investigator may be enrolled).
10. For women of childbearing potential, a negative urine or serum pregnancy test within 3 days prior to the first study drug administration (Cycle 1 Day 1) is required. If the urine pregnancy test result is equivocal, a serum test must be performed. Women of non-childbearing potential are defined as those who are postmenopausal for at least 1 year, or who have undergone surgical sterilization or hysterectomy;
11. All participants (male and female) with reproductive potential must agree to use highly effective contraception (with an annual failure rate <1%) throughout the study period and for at least 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy).

排除标准：

1.已知肝胆管细胞癌、肉瘤样肝细胞癌、肝混合细胞癌及纤维板层细胞癌；5 年内或同时患有除肝细胞癌之外的其它活动性恶性肿瘤。已治愈的局限性肿瘤，如皮肤基底细胞癌、皮肤鳞癌、表浅膀胱癌、前列腺原位癌、宫颈原位癌、乳腺原位癌等可以入组； 2.入组后接受超过 1 次消融治疗的患者（注：允许患者接受第二次挽救性消融，第二次挽救性消融需在首次消融术后 4周内完成）； 3.入组后接受过超过 1 次 TACE 治疗； 4.随机时存在病灶残余，复发及转移证据； 5.既往接受过下列疗法：抗PD-1、抗PD-L1或抗PD-L2药物或者针对另一种刺激或协同抑制T细胞受体（例如，CTLA-4、OX-40、CD137）的药物； 6.首次给药前2周内接受过具有抗肿瘤适应症的中成药或免疫调节作用的药物（包括胸腺肽、干扰素、白介素）系统性全身治疗； 7.有临床症状的中度、重度腹水即需要治疗性的穿刺、引流者或 Child-Pugh 评分>2（仅影像学显示少量腹水但不伴有临床症状者除外）；不受控制或中等量及以上的胸腔积液、心包积液； 8.有肝性脑病病史者； 9.存在活动性自身免疫病或有自身免疫病病史且可能复发（包括但不局限于：自身免疫性肝炎、间质性肺炎、葡萄膜炎、肠炎、垂体炎、血管炎、肾炎、甲状腺功能亢进、甲状腺功能降低[仅通过激素替代治疗可以控制的受试者可纳入]）；受试者患有无需系统治疗的皮肤病如白癜风、银屑病、脱发，接受胰岛素治疗的经控制的 I 型糖尿病或在童年期哮喘已完全缓解，成人后无需任何干预的可纳入；需要支气管扩张剂进行医学干预的哮喘患者则不能纳入； 10.目前伴有间质性肺炎或间质性肺病，或既往有需激素治疗的间质性肺炎或间质性肺病病史者，或其他可能干扰免疫相关肺毒性判断和处理的肺纤维化、机化性肺炎（例如，闭塞性细支气管炎）、尘肺、药物相关肺炎、特发性肺炎或在筛选期胸部计算机断层扫描（CT）图上可见活动性肺炎证据或肺功能严重受损的受试者，允许放射野曾有放射性肺炎；活动性结核； 11.已知对本研究药物替雷利珠单抗活性成分或辅料过敏者; 12.已知人类免疫缺陷病毒（HIV）感染史（即HIV 1/2抗体阳性）； 13.未经治疗的活动性乙肝（定义为HBsAg阳性同时检测到HBV-DNA拷贝数大于所在研究中心检验科正常值上限）；注：符合下列标准的乙肝受试者亦可入组： 1)首次给药前HBV病毒载量<1000拷贝/ml（200 IU/ml），受试者应在整个研究化疗药物治疗期间接受抗HBV治疗避免病毒再激活 2)对于抗HBc（+）、HBsAg（-）、抗HBs（-）和HBV病毒载量（-）的受试者，不需要接受预防性抗HBV治疗，但是需要密切监测病毒再激活 14.活动性的HCV感染受试者（HCV抗体阳性且HCV-RNA水平高于检测下限）； 15.妊娠或哺乳期妇女； 16.存在任何严重或不能控制的全身性疾病，例如： 1)静息心电图在节律、传导或形态上出现有重大且症状严重难以控制的异常，如完全性左束支传导阻滞，Ⅱ度以上心脏传导阻滞，室性心律失常或心房颤动； 2)不稳定型心绞痛，充血性心力衰竭，纽约心脏病协会（NYHA）分级≥ 2 级的慢性心衰； 3)在入选治疗前6个月内发生过任何动脉血栓、栓塞或缺血，如心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作等； 4)血压控制不理想（收缩压＞140 mmHg，舒张压＞90 mmHg）； 5)首次给药前1年内存在需要糖皮质激素治疗的非感染性肺炎病史，或当前存在临床活动性间质性肺病； 6)存在需要全身性治疗的活动性或未能控制的感染； 7)存在临床活动性憩室炎、腹腔脓肿、胃肠道梗阻； 8)肝脏疾病如肝硬化、失代偿性肝病、急性或慢性活动性肝炎； 9)糖尿病控制不佳（空腹血糖（FBG）＞10mmol/L）； 10)尿常规提示尿蛋白≥++，且证实24小时尿蛋白定量＞1.0 g者； 11)存在精神障碍且无法配合治疗的患者； 17.有可能干扰试验结果、妨碍受试者全程参与研究的病史或疾病证据、治疗或实验室检查值异常，或研究者认为其他不适合入组的情况研究者认为存在其他潜在风险不适合参加本研究。

Exclusion criteria：

1.Known combined hepatocellular-cholangiocarcinoma, sarcomatoid HCC, mixed HCC, or fibrolamellar carcinoma; presence of another active malignancy within the past 5 years or concurrently, except for adequately treated localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, cervix, or breast; 2. Patients who undergo more than one ablation after enrollment (note: a second salvage ablation is permitted if performed within 4 weeks after the first ablation); 3. Patients who receive more than one transarterial chemoembolization (TACE) procedure after enrollment; 4. Evidence of residual disease, recurrence, or metastasis at randomization; 5. Prior therapy with anti–PD-1, anti–PD-L1, anti–PD-L2 antibodies, or agents targeting other stimulatory or co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137); 6. Systemic treatment with traditional Chinese medicines with anti-tumor indications or immunomodulatory agents (including thymosin, interferon, interleukin) within 2 weeks prior to first dose; 7. Symptomatic moderate or severe ascites requiring therapeutic paracentesis or drainage, or Child–Pugh score >2 (patients with imaging evidence of small-volume ascites without clinical symptoms may be enrolled); uncontrolled or moderate-to-severe pleural effusion or pericardial effusion; 8. History of hepatic encephalopathy; 9. Active autoimmune disease or history of autoimmune disease that may relapse (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, colitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism [patients controlled on hormone replacement therapy may be included]); patients with stable, non–systemically treated skin conditions such as vitiligo, psoriasis, alopecia, controlled type I diabetes mellitus on insulin therapy, or childhood asthma completely resolved without adult intervention may be enrolled; patients with asthma requiring bronchodilator therapy are excluded; 10. Current interstitial pneumonia or interstitial lung disease, history of steroid-requiring interstitial pneumonia or ILD, or other lung conditions that may interfere with the assessment and management of immune-related pneumonitis (e.g., pulmonary fibrosis, organizing pneumonia such as bronchiolitis obliterans, pneumoconiosis, drug-induced pneumonitis, idiopathic pneumonia); evidence of active pneumonia on screening CT or severely impaired pulmonary function; active tuberculosis; prior radiation pneumonitis is permitted if confined to the radiation field; 11. Known allergy to the active ingredient or excipients of toripalimab; 12. Known history of human immunodeficiency virus (HIV) infection (HIV-1/2 antibody positive); 13. Untreated active hepatitis B infection, defined as HBsAg-positive with HBV DNA above the upper limit of normal (ULN) for the testing laboratory. Patients may be eligible if they meet the following criteria: HBV DNA <1000 copies/mL (200 IU/mL) prior to first dose, with antiviral therapy administered throughout chemotherapy to prevent reactivation; For anti-HBc(+), HBsAg(–), anti-HBs(–), and HBV DNA(–) patients, prophylactic antiviral therapy is not required, but close monitoring for viral reactivation is necessary. 14. Active hepatitis C infection, defined as HCV antibody positive with HCV RNA above the lower limit of detection; 15. Pregnant or breastfeeding women; 16. Presence of any severe or uncontrolled systemic disease, including but not limited to: Significant, symptomatic, and uncontrolled abnormalities on resting ECG in rhythm, conduction, or morphology (e.g., complete left bundle branch block, grade ≥II heart block, ventricular arrhythmias, or atrial fibrillation). Unstable angina, congestive heart failure, or chronic heart failure classified as New York Heart Association (NYHA) class >=2. Arterial thromboembolic or ischemic events (e.g., myocardial infarction, unstable angina, stroke, transient ischemic attack) within 6 months prior to enrollment. Poorly controlled hypertension (systolic BP >140 mmHg or diastolic BP >90 mmHg); History of non-infectious pneumonitis requiring corticosteroid therapy within 1 year prior to first dose, or current active interstitial lung disease; Active or uncontrolled systemic infection requiring systemic therapy; Clinically active diverticulitis, intra-abdominal abscess, or gastrointestinal obstruction; Liver diseases such as cirrhosis, decompensated liver disease, or acute/chronic active hepatitis; Poorly controlled diabetes mellitus (fasting blood glucose >10 mmol/L); Proteinuria >=++ on dipstick confirmed by 24-hour urine protein >1.0 g. Psychiatric disorders that interfere with compliance. 17. Any medical history, condition, therapy, or laboratory abnormality that may interfere with trial results, impede full participation, or pose unacceptable risk as judged by the investigator.

研究实施时间：

Study execute time：

从 From 2025-09-30 00:00:00至 To 2028-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-10-09 00:00:00 至 To 2026-12-31 00:00:00

干预措施：

Interventions：

组别：	观察组	样本量：	30
Group：	Observation group	Sample size：	30
干预措施：	无	干预措施代码：
Intervention：	None	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	吉林	市(区县)：	延吉
Country：	China	Province：	Jilin	City：	Yanji
单位(医院)：	延边大学附属医院	单位级别：	三级甲等综合医院
Institution hospital：	Affiliated Hospital of Yanbian University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	无进展生存期	指标类型：	主要指标
Outcome：	Progression-Free Survival,PFS	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	总生存期	指标类型：	次要指标
Outcome：	Overall Survival.OS	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	局部复发	指标类型：	次要指标
Outcome：	Local Tumor Progression,LTP	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	肝内远处复发	指标类型：	次要指标
Outcome：	Intrahepatic Distant Recurrence,IDR	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	肝外复发时间	指标类型：	次要指标
Outcome：	Time to Extrahepatic Dissemination,TTED	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	不良事件	指标类型：	次要指标
Outcome：	Adverse Events,AEs	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	影像学可测量病灶	组织：
Sample Name：	The lesion can be measured by imaging	Tissue：
人体标本去向	其它	说明
Fate of sample：	0thers	Note：

标本中文名：	血液	组织：
Sample Name：	blood	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age		岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

未使用

Randomization Procedure (please state who generates the random number sequence and by what method)：

Not used

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：	N/A
Blinding：	N/A
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

是否共享原始数据： IPD sharing	否No
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	未说明
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Not stated
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	病例记录表
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	CRF
数据与安全监察委员会： Data and Safety Monitoring Committee：	暂未确定/Not yet
注册人： Name of Registration：	2025-09-30 08:27:03